rs1085307120
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PVS1PM2PP3_StrongPP5
The NM_025009.5(CEP135):c.1473+1G>A variant causes a splice donor change. The variant allele was found at a frequency of 0.000000697 in 1,434,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
CEP135
NM_025009.5 splice_donor
NM_025009.5 splice_donor
Scores
5
1
1
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 6.63
Genes affected
CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 15 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 4-55974970-G-A is Pathogenic according to our data. Variant chr4-55974970-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 417785.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP135 | NM_025009.5 | c.1473+1G>A | splice_donor_variant | ENST00000257287.5 | |||
CEP135 | XM_005265788.5 | c.402+1G>A | splice_donor_variant | ||||
CEP135 | XM_006714055.4 | c.1440+1G>A | splice_donor_variant | ||||
CEP135 | XM_011534412.2 | c.-58+3562G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP135 | ENST00000257287.5 | c.1473+1G>A | splice_donor_variant | 1 | NM_025009.5 | P1 | |||
CEP135 | ENST00000506202.1 | n.1423+1G>A | splice_donor_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1434302Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 710728
GnomAD4 exome
AF:
AC:
1
AN:
1434302
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
710728
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Microcephaly 8, primary, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 29, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at